Metastasis, the dissemination of malignant diseases, is the most devastating aspect of neoplasia, since it is responsible for most therapeutic failures in clinical oncology. Studies with cell lines derived from the mouse melanoma B16 highlighted one distinctive feature of cell variants exhibiting high metastatic potential--their ability to aggregate with like cells (homotypic aggregation) and with unlike cells (heterotypic aggregation). Although it is conceivable that surface properties of tumor cells play a role in the above intercellular interactions, the molecular basis for these phenomena remains to be elucidated. Recently, we found that various cultured human and murine tumor cells, including the B16-F1 melanoma and the UV-2237P fibrosarcoma, possess cell surface sugar-binding proteins (lectins). Such molecules are eminently suitable for mediating cognitive intercellular adhesion by binding with carbohydrate-containing surface membrane components on adjacent cells. It is plausible to assume that the presence of lectin on the surface of metastatic tumor cells that reach the circulation can control processes such as embolization and arrest in a particular organ. We propose to investigate the possible role of tumor cell surface lectins in the pathogenesis of cancer metastasis. Specifically, we will employ two established model systems of experimental metastasis consisting of cell variants, derived from the B16-F1 melanoma and the UV-2237P fibrosarcoma, which include highly metastatic, poorly metastatic, and non-metastatic tumor cells. First, we will investigate the presence, amount, physicochemical properties, and sugar-binding specificity of the lectins that will be purified from the various cells. Second, we will identify, isolate, and characterize cell membrane glycoconjugates of tumor cells as well as of host cells (e.g., platelets and lymphocytes) which may serve as ligands for the lectins. Third, we will attempt to alter the in vivo behavior of tumor cells by modulating cell surface lectins or their putative ligands in target organs. It is expected that the information gained from these studies will establish the role of tumor-cell surface lectins and lectin-reactive glycoconjugates in the various steps of the metastatic process. (A)